Bidirectional affinity

Interaction between ephrin receptor EphB4 and its ligand EFNB2 mediates bidirectional signaling important for cancer: forward EFNB2-to-EphB4 signaling that is tumor suppressive, and reverse EphB4-to-EFNB2 signaling that promotes angiogenesis important for tumor growth and metastasis. Molecular agents targeting these forward and reverse signals of EphB4-EFNB2 interaction can be used to probe the molecular mechanisms of these complex signaling pathways and develop new anticancer therapeutics. In this study, we applied a bivalent ligand design strategy to synthesize a novel dimeric peptide based on an antagonist TNYL-RAW...

BACKGROUND: MicroRNAs (miRNAs) have been confirmed to be inextricably linked to the emergence of human complex diseases. The identification of the disease-related miRNAs has gradually become a routine way to unveil the genetic mechanisms of examined disorders. METHODS: In this study, a method BLNIMDA based on a weighted bi-level network was proposed for predicting hidden associations between miRNAs and diseases. For this purpose, the known associations between miRNAs and diseases as well as integrated similarities between miRNAs and diseases are mapped into a bi-level network...

The promoter is a DNA sequence recognized, bound and transcribed by RNA polymerase. It is usually located at the upstream or 5'end of the transcription start site (TSS). Studies have shown that the structure of the promoter affects its affinity for RNA polymerase, thus affecting the level of gene expression. Therefore, the correct identification of core promoter and common structural gene is of great significance in the field of biomedicine. At present, many methods have been proposed to improve the accuracy of promoter recognition, but the performances still need to be further improved...

SARS-CoV-2, the virus responsible for COVID-19 in humans, can efficiently infect a large number of animal species. Like any virus, and particularly RNA viruses, SARS-CoV-2 undergoes mutations during its life cycle some of which bring a selective advantage, leading to the selection of a given lineage. Minks are very susceptible to SARS-CoV-2 and owing to their presence in mass rearing, they make a good model for studying the relative importance of mutations in viral adaptation to host species. Variants, such as the mink-selected SARS-CoV-2 Y453F and D614G or H69del/V70del, Y453F, I692V and M1229I were identified in humans after spreading through densely caged minks...

The rapidly accelerating characterization of RNA tertiary structures has revealed their pervasiveness and active roles in human diseases. Small molecule-mediated modulation of RNA tertiary structures constitutes an attractive avenue for the development of tools for therapeutically targeting and/or uncovering the pathways associated with these RNA motifs. This potential has been highlighted by targeting of the triple helix present at the 3'-end of the noncoding RNA MALAT1, a transcript implicated in several human diseases...

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease, with approximately 10% of cases associated with genetic variants. Recent genetic studies have reported pathogenic variants in the TBX4 gene in patients with PAH, especially in patients with childhood-onset of the disease, but the pathogenesis of PAH caused by TBX4 variant has not been fully uncovered. METHODS: We analysed the TBX4 gene in 75 Japanese patients with sporadic or familial PAH using a PCR-based bidirectional sequencing method...

Histaminergic (HA) neurons are located in the tuberomamillary nucleus (TMN) of the posterior hypothalamus, from where they project throughout the whole brain to control wakefulness. We examined the effects of Nα -oleoylhistamine (OLHA), a non-enzymatic condensation product of oleic acid (OLA) and histamine, on activity of mouse HA neurons in brain slices. OLHA bidirectionally modulated the firing of HA neurons. At 10 nM OLHA inhibited or had no action, whereas at 1 μM it evoked excitatory and inhibitory responses...

Noise affects all biological processes from molecules to cells, organisms and populations. Although the effect of noise on these processes is highly variable, evidence is accumulating which shows natural stochastic fluctuations (noise) can facilitate biological functions. Herein, we investigate the effect of noise on the transport of intermediate filaments in cells by comparing the stochastic and deterministic formalizations of the bidirectional transport of intermediate filaments, long elastic polymers transported along microtubules by antagonistic motor proteins Dallon et al...

The rapidly increasing characterization of RNA tertiary structures has revealed their pervasiveness and active roles in human diseases. Therefore, small molecule-mediated modulation of RNA tertiary structures constitutes an attractive avenue for the development of tools for both therapeutically targeting and/or uncovering the pathways associated with these RNA motifs. This potential has been highlighted by preliminary targeting of the triple helix present at the 3'-end of the non-coding RNA MALAT1, a transcript implicated in several human diseases...

The signaling pathways and cellular functions regulated by the four Numb-associated kinases are largely unknown. We reported that AAK1 and GAK control intracellular trafficking of RNA viruses and revealed a requirement for BIKE in early and late stages of dengue virus (DENV) infection. However, the downstream targets phosphorylated by BIKE have not yet been identified. Here, to identify BIKE substrates, we conducted a barcode fusion genetics-yeast two-hybrid screen and retrieved publicly available data generated via affinity-purification mass spectrometry...

Melatonin is a neurohormone that modulates several physiological functions in mammals through the activation of melatonin receptor type 1 and 2 (MT1 and MT2 ). The melatonergic system is an emerging therapeutic target for new pharmacological interventions in the treatment of sleep and mood disorders; thus, imaging tools to further investigate its role in the brain are highly sought-after. We aimed to develop selective radiotracers for in vivo imaging of both MT1 and MT2 by positron emission tomography (PET)...

A shutdown-functionalized lithium-ion battery separator plays a pivotal role in preventing thermal runaway as cells experience electrical abuse, overcharge, and external short circuit. In this article, the trilayer separator endowed with shutdown function was fabricated by ingenious co-extrusion and bidirectional drawing based on the nano-Al2 O3 coating online construction during the β-iPP cavitation process. The middle layer composed of nano-Al2 O3 , polyethylene, and polypropylene offers a shutdown temperature of 130 °C, and skin polypropylene layers with nano-Al2 O3 coating hold optimized dimensional stability below the meltdown temperature...

Mediating the redox kinetics of polysulfides is a promising strategy to mitigate the shuttling and sluggish conversion of polysulfides for practical application of lithium-sulfur (Li-S) batteries. Herein, novel TiH2 nanodots (THNDs) fabricated by sonication-assisted liquid-phase exfoliation are used as bifunctional electrocatalysts for Li-S batteries. Both experimental and theoretical results reveal that THNDs can not only provide a strong chemical affinity to polysulfides but also bidirectionally promote the precipitation/decomposition of Li2 S from/to polysulfides during the discharge/charge process, thus effectively suppressing the shuttle effect and improving the redox kinetics of polysulfides...

Schizophrenia is a chronic psychiatric disorder that may lead to epilepsy. However, there are limited findings on the issues. This narrative review aimed to provide a practical perspective on epilepsy in patients with schizophrenia using the current treatment systems for epilepsy. While there has been a debate on the relationship between epilepsy and schizophrenia, i.e., antagonism, affinity, and coincidence, recent large cohort studies have revealed a high frequency of epilepsy in patients with schizophrenia (4-5 times higher than that of general population)...

This paper studies the problem of the dynamic scaling and load balancing of transparent virtualized network functions (VNFs). It analyzes different particularities of this problem, such as loop avoidance when performing scaling-out actions, and bidirectional flow affinity. To address this problem, a software-defined networking (SDN)-based solution is implemented consisting of two SDN controllers and two OpenFlow switches (OFSs). In this approach, the SDN controllers run the solution logic (i.e., monitoring, scaling, and load-balancing modules)...

During pregnancy, there are several metabolic changes and an alteration in the composition of microorganisms that inhabit the oral cavity, with an increase in pathogenic bacteria that promote the onset of gingival diseases. This review is based on research in reference to the PICO model (Problem/Intervention/Comparison/Outcome), related to changes in the oral microbiome of pregnant women and possible oral consequences in patients with COVID-19. The results showed a growth of some pathogenic bacteria in pregnant women, including Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum , and the selective growth of the Prevotella intermedia , Porphyromonas gingivalis and Tannerella species, probably due to the fact that these bacteria use progesterone as a source of nutrition...

The magnetic bistability of spin-crossover (SCO) materials is highly appealing for applications as molecular switches and information storage. However, switching of the spin state around room temperature remains challenging. In this work, we reported the successful manipulation of the spin states of two iron(II) complexes ( 1-Fe and 2-Fe ) based on pyridylacylhydrazone ligands in manifold ways. Both complexes are stabilized in the low-spin (LS) state at room temperature because of the strong ligand-field strength imposed by the ligands...

It has long been known that there is a special affinity of psoriasis for the scalp: Here, it occurs most frequently, lesions terminate sharply in frontal skin beyond the hair line and are difficult to treat. Yet, surprisingly, scalp psoriasis only rarely causes alopecia, even though the pilosebaceous unit clearly is affected. Here, we systematically explore the peculiar, insufficiently investigated connection between psoriasis and growing (anagen) terminal scalp hair follicles (HFs), with emphasis on shared regulatory mechanism and therapeutic targets...

This study unites six popular machine learning approaches to enhance the prediction of a molecular binding affinity between receptors (large protein molecules) and ligands (small organic molecules). Here we examine a scheme where affinity of ligands is predicted against a single receptor - human thrombin, thus, the models consider ligand features only. However, the suggested approach can be repurposed for other receptors. The methods include Support Vector Machine, Random Forest, CatBoost, feed-forward neural network, graph neural network, and Bidirectional Encoder Representations from Transformers...

Integrin activation by the intracellular adaptor proteins talin1 and kindlin-3 is essential for lymphocyte adhesion. These adaptors cooperatively control integrin activation through bidirectional (inside-out and outside-in) activation signals. Using single-molecule measurements, we revealed the distinct dynamics of talin1 and kindlin-3 interactions with the integrin LFA1 (αLβ2) and their functions in LFA1 activation and LFA1-mediated adhesion. The kinetics of talin1 binding to the tail of the β2 subunit corresponded to those of LFA1 binding to its ligand ICAM1...